Money Trouble Ends Pursuit of Cancer Drug

Balance, after 11 years and $25 million, runs out of cash to seek FDA approval for Libra.

A truck rolled out of an industrial strip mall near the 10 Freeway in Santa Monica, hauling the largest shipment ever to leave tiny Balance Pharmaceuticals Inc.: seven chemical drums containing thousands of doses of an investigational cancer-prevention drug called Libra.

It took Balance 11 years and nearly $25 million to reach that day -- its last in business. The drug stockpile that left the warehouse last month didn't go to patients -- it went to an incinerator.

Balance lost a race faced by most of the nation's 1,400 biotech firms: to develop a drug before the cash runs out. The biotech industry collectively loses billions of dollars a year pursuing complicated treatments that rarely make it to market. Driving them is the success of a few biotech giants, such as Amgen Inc. and Genentech Inc., that have hit the biotech lottery with a handful of multibillion-dollar drugs.

Balance's experimental drug was a once-daily hormone nasal spray developed to prevent breast cancer. In theory, Libra worked by inducing chemical menopause to slow the division of cells in the breast. Scientists believed this would reduce the genetic mutations that in turn triggered breast cancer.

The results of human tests were encouraging, but Balance needed an additional $50 million to finish clinical trials.

"I never believed it would come to this," said Chief Operating Officer AnnaMarie Daniels, whose husband, John Daniels, a USC oncologist, co-founded the company. Today, what remains of Balance is stored at the couple's home: many boxes of documents and a small stash of Libra in their refrigerator -- enough for one more clinical trial.

One of the biggest disappointments from Balance's failure wasn't felt by its investors but by patients who volunteered to take the drug. Jodee Brooks, 42, of Orange, was on Libra for a year. Breast cancer runs in her family. Her sister had breast cancer and endured surgery, radiation and chemotherapy. Her mother and great-grandmother also had breast cancer.

So Brooks, the mother of two boys, and 13 other high-risk women used the Libra spray for a year in a clinical trial. Before they started on the drug, their mammograms showed fibrous clumps -- indicators associated with high cancer risk. After a year on Libra, the clumps were gone.

Women in the study complained about hot flashes and other menopausal symptoms, but none stopped taking Libra. Brooks said she once raced to hide in a department store dressing room after she broke out in a sweat. But her symptoms from Libra were trivial compared with what her sister suffered, she said.

"I wanted to keep taking it. It made me feel protected," Brooks said.

After the drug trial, four women chose to have their healthy breasts or ovaries removed in hopes of avoiding breast cancer -- among the few choices available. Their doctor, Jeffrey Weitzel of City of Hope National Medical Center, said the clinical trial was too preliminary to establish Libra as an alternative to the surgeries -- an option he called "draconian."

Balance grew out of two decades of research by Malcolm Pike, a USC medical statistician, who linked breast cancer risk and exposure to sex hormones -- now a widely accepted notion. In 1992, Pike teamed up with John Daniels and another USC oncologist, Darcy Spicer, to turn his theories into a commercial product.

From the start, the company ran into unforeseen obstacles. It took several years to develop the Libra nasal spray, much longer than expected. Later, regulatory delays and miscalculations about drug tests tripled the cost of clinical trials.

"I have been an academic my whole life," said Pike, 68. "I really didn't understand the enormous gamble ... and how much money is involved."

Pike dreamed of marketing Libra as a contraceptive -- a use that would have made it available to thousands of women. To him, Libra offered an improvement on the birth control pill, which does not lower breast cancer risk. However, to sell Libra as a contraceptive, Balance would have had to test it in more than 1,000 women at a cost of $100 million or more.

Fibroid Treatment

In 1995, Balance was just a young company that had raised less than $4 million from family and friends. So the partners needed to lower their sights and find a less expensive way to bring Libra to market.

They decided to try Libra in women with fibroids, lumps of tissue that grow in the uterus and account for 240,000 hysterectomies a year. Fed by hormones, fibroids can cause pain and bleeding. They made ideal targets for Libra.

Clinical tests started in 1996 and showed promising results. Women in the study reported less pain and bleeding.

Fibroids account for 40% of hysterectomies, surgeries in which the uterus is removed, said Dr. Anthony Scialli, director of obstetrics and gynecology at Georgetown University Medical School. "It is a big problem."